{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,6]],"date-time":"2026-11-06T23:37:52Z","timestamp":1794008272399,"version":"4.8.0"},"reference-count":41,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2024,9,6]],"date-time":"2024-09-06T00:00:00Z","timestamp":1725580800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"},{"start":{"date-parts":[[2024,9,6]],"date-time":"2024-09-06T00:00:00Z","timestamp":1725580800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Nat Commun"],"DOI":"10.1038\/s41467-024-52107-w","type":"journal-article","created":{"date-parts":[[2024,9,6]],"date-time":"2024-09-06T06:02:34Z","timestamp":1725602554000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":41,"title":["Cryo-EM structures of Candida albicans Cdr1 reveal azole-substrate recognition and inhibitor blocking mechanisms"],"prefix":"10.1038","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3797-6870","authenticated-orcid":false,"given":"Ying","family":"Peng","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan","family":"Lu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-7850-7655","authenticated-orcid":false,"given":"Hui","family":"Sun","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-3893-7942","authenticated-orcid":false,"given":"Jinying","family":"Ma","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7662-1925","authenticated-orcid":false,"given":"Xiaomei","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-8619-2780","authenticated-orcid":false,"given":"Xiaodan","family":"Han","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhixiong","family":"Fang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-6452-1870","authenticated-orcid":false,"given":"Junming","family":"Tan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yingchen","family":"Qiu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4455-2064","authenticated-orcid":false,"given":"Tingting","family":"Qu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2293-7112","authenticated-orcid":false,"given":"Meng","family":"Yin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9054-3313","authenticated-orcid":false,"given":"Zhaofeng","family":"Yan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,9,6]]},"reference":[{"key":"52107_CR1","doi-asserted-by":"publisher","first-page":"57","DOI":"10.3390\/jof3040057","volume":"3","author":"F Bongomin","year":"2017","unstructured":"Bongomin, F., Gago, S., Oladele, R. O. & Denning, D. W. Global and multi-national prevalence of fungal diseases-estimate precision. J. Fungi (Basel) 3, 57 (2017).","journal-title":"J. Fungi (Basel)"},{"key":"52107_CR2","doi-asserted-by":"publisher","first-page":"753","DOI":"10.1146\/annurev-micro-030117-020345","volume":"71","author":"N Robbins","year":"2017","unstructured":"Robbins, N., Caplan, T. & Cowen, L. E. Molecular evolution of antifungal drug resistance. Annu Rev. Microbiol. 71, 753\u2013775 (2017).","journal-title":"Annu Rev. Microbiol."},{"key":"52107_CR3","doi-asserted-by":"publisher","first-page":"833","DOI":"10.1007\/s40265-019-01127-8","volume":"79","author":"LL Benitez","year":"2019","unstructured":"Benitez, L. L. & Carver, P. L. Adverse effects associated with long-term administration of azole antifungal agents. Drugs 79, 833\u2013853 (2019).","journal-title":"Drugs"},{"key":"52107_CR4","doi-asserted-by":"publisher","first-page":"143","DOI":"10.15698\/mic2020.06.718","volume":"7","author":"K Kainz","year":"2020","unstructured":"Kainz, K., Bauer, M. A., Madeo, F. & Carmona-Gutierrez, D. Fungal infections in humans: the silent crisis. Micro. Cell 7, 143\u2013145 (2020).","journal-title":"Micro. Cell"},{"key":"52107_CR5","doi-asserted-by":"publisher","first-page":"367","DOI":"10.1126\/science.1159746","volume":"321","author":"BC Monk","year":"2008","unstructured":"Monk, B. C. & Goffeau, A. Outwitting multidrug resistance to antifungals. Science 321, 367\u2013369 (2008).","journal-title":"Science"},{"key":"52107_CR6","doi-asserted-by":"publisher","first-page":"2676","DOI":"10.1128\/AAC.45.10.2676-2684.2001","volume":"45","author":"S Perea","year":"2001","unstructured":"Perea, S. et al. Prevalence of molecular mechanisms of resistance to azole antifungal agents in Candida albicans strains displaying high-level fluconazole resistance isolated from human immunodeficiency virus-infected patients. Antimicrob. Agents Chemother. 45, 2676\u20132684 (2001).","journal-title":"Antimicrob. Agents Chemother."},{"key":"52107_CR7","doi-asserted-by":"publisher","first-page":"382","DOI":"10.1128\/CMR.11.2.382","volume":"11","author":"TC White","year":"1998","unstructured":"White, T. C., Marr, K. A. & Bowden, R. A. Clinical, cellular, and molecular factors that contribute to antifungal drug resistance. Clin. Microbiol Rev. 11, 382\u2013402 (1998).","journal-title":"Clin. Microbiol Rev."},{"key":"52107_CR8","doi-asserted-by":"publisher","first-page":"68","DOI":"10.3390\/jof7020068","volume":"7","author":"A Banerjee","year":"2021","unstructured":"Banerjee, A. et al. Directed mutational strategies reveal drug binding and transport by the MDR transporters of Candida albicans. J. Fungi (Basel) 7, 68 (2021).","journal-title":"J. Fungi (Basel)"},{"key":"52107_CR9","doi-asserted-by":"publisher","first-page":"557","DOI":"10.1038\/s41579-022-00720-1","volume":"20","author":"MC Fisher","year":"2022","unstructured":"Fisher, M. C. et al. Tackling the emerging threat of antifungal resistance to human health. Nat. Rev. Microbiol 20, 557\u2013571 (2022).","journal-title":"Nat. Rev. Microbiol"},{"key":"52107_CR10","doi-asserted-by":"publisher","first-page":"223","DOI":"10.1007\/s11046-014-9749-1","volume":"177","author":"N Martins","year":"2014","unstructured":"Martins, N., Ferreira, I. C., Barros, L., Silva, S. & Henriques, M. Candidiasis: predisposing factors, prevention, diagnosis and alternative treatment. Mycopathologia 177, 223\u2013240 (2014).","journal-title":"Mycopathologia"},{"key":"52107_CR11","doi-asserted-by":"publisher","first-page":"291","DOI":"10.1128\/CMR.00051-08","volume":"22","author":"RD Cannon","year":"2009","unstructured":"Cannon, R. D. et al. Efflux-mediated antifungal drug resistance. Clin. Microbiol Rev. 22, 291\u2013321 (2009).","journal-title":"Clin. Microbiol Rev."},{"key":"52107_CR12","doi-asserted-by":"publisher","first-page":"127","DOI":"10.1016\/j.fgb.2009.10.007","volume":"47","author":"E Lamping","year":"2010","unstructured":"Lamping, E. et al. Fungal PDR transporters: Phylogeny, topology, motifs and function. Fungal Genet Biol. 47, 127\u2013142 (2010).","journal-title":"Fungal Genet Biol."},{"key":"52107_CR13","doi-asserted-by":"publisher","first-page":"523","DOI":"10.1091\/mbc.9.2.523","volume":"9","author":"R Egner","year":"1998","unstructured":"Egner, R., Rosenthal, F. E., Kralli, A., Sanglard, D. & Kuchler, K. Genetic separation of FK506 susceptibility and drug transport in the yeast Pdr5 ATP-binding cassette multidrug resistance transporter. Mol. Biol. Cell 9, 523\u2013543 (1998).","journal-title":"Mol. Biol. Cell"},{"key":"52107_CR14","doi-asserted-by":"publisher","first-page":"3366","DOI":"10.1128\/AAC.45.12.3366-3374.2001","volume":"45","author":"K Nakamura","year":"2001","unstructured":"Nakamura, K. et al. Functional expression of Candida albicans drug efflux pump Cdr1p in a Saccharomyces cerevisiae strain deficient in membrane transporters. Antimicrob. Agents Chemother. 45, 3366\u20133374 (2001).","journal-title":"Antimicrob. Agents Chemother."},{"key":"52107_CR15","doi-asserted-by":"publisher","first-page":"1361","DOI":"10.1128\/EC.2.6.1361-1375.2003","volume":"2","author":"S Shukla","year":"2003","unstructured":"Shukla, S. et al. Functional characterization of Candida albicans ABC transporter Cdr1p. Eukaryot. Cell 2, 1361\u20131375 (2003).","journal-title":"Eukaryot. Cell"},{"key":"52107_CR16","doi-asserted-by":"publisher","first-page":"69","DOI":"10.1016\/j.ijantimicag.2006.02.016","volume":"28","author":"PH Gao","year":"2006","unstructured":"Gao, P. H. et al. Drug susceptibilities of yeast cells are affected when expressing mutant Candida albicans drug resistance protein. Int J. Antimicrob. Agents 28, 69\u201374 (2006).","journal-title":"Int J. Antimicrob. Agents"},{"key":"52107_CR17","doi-asserted-by":"publisher","first-page":"1344","DOI":"10.1128\/AAC.00926-08","volume":"53","author":"S Tsao","year":"2009","unstructured":"Tsao, S., Rahkhoodaee, F. & Raymond, M. Relative contributions of the Candida albicans ABC transporters Cdr1p and Cdr2p to clinical azole resistance. Antimicrob. Agents Chemother. 53, 1344\u20131352 (2009).","journal-title":"Antimicrob. Agents Chemother."},{"key":"52107_CR18","doi-asserted-by":"publisher","first-page":"405","DOI":"10.1099\/00221287-143-2-405","volume":"143","author":"D Sanglard","year":"1997","unstructured":"Sanglard, D., Ischer, F., Monod, M. & Bille, J. Cloning of Candida albicans genes conferring resistance to azole antifungal agents: characterization of CDR2, a new multidrug ABC transporter gene. Microbiol. (Read.) 143, 405\u2013416 (1997).","journal-title":"Microbiol. (Read.)"},{"key":"52107_CR19","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-021-25574-8","volume":"12","author":"A Harris","year":"2021","unstructured":"Harris, A. et al. Structure and efflux mechanism of the yeast pleiotropic drug resistance transporter Pdr5. Nat. Commun. 12, 5254 (2021).","journal-title":"Nat. Commun."},{"key":"52107_CR20","doi-asserted-by":"publisher","first-page":"1154","DOI":"10.1128\/EC.00137-15","volume":"14","author":"R Prasad","year":"2015","unstructured":"Prasad, R., Banerjee, A., Khandelwal, N. K. & Dhamgaye, S. The ABCs of Candida albicans Multidrug Transporter Cdr1. Eukaryot. Cell 14, 1154\u20131164 (2015).","journal-title":"Eukaryot. Cell"},{"key":"52107_CR21","doi-asserted-by":"publisher","first-page":"e01146","DOI":"10.1128\/AAC.01146-18","volume":"63","author":"K Tanabe","year":"2019","unstructured":"Tanabe, K. et al. FK506 resistance of saccharomyces cerevisiae Pdr5 and Candida albicans Cdr1 involves mutations in the transmembrane domains and extracellular loops. Antimicrob. Agents Chemother. 63, e01146\u201318 (2019).","journal-title":"Antimicrob. Agents Chemother."},{"key":"52107_CR22","doi-asserted-by":"publisher","first-page":"747","DOI":"10.1111\/j.1365-2958.2012.08140.x","volume":"85","author":"K Niimi","year":"2012","unstructured":"Niimi, K. et al. Specific interactions between the Candida albicans ABC transporter Cdr1p ectodomain and a D-octapeptide derivative inhibitor. Mol. Microbiol. 85, 747\u2013767 (2012).","journal-title":"Mol. Microbiol."},{"key":"52107_CR23","doi-asserted-by":"publisher","first-page":"873","DOI":"10.1128\/AAC.02040-12","volume":"57","author":"LV Silva","year":"2013","unstructured":"Silva, L. V. et al. Milbemycins: more than efflux inhibitors for fungal pathogens. Antimicrob. Agents Chemother. 57, 873\u2013886 (2013).","journal-title":"Antimicrob. Agents Chemother."},{"key":"52107_CR24","doi-asserted-by":"publisher","first-page":"24480","DOI":"10.1074\/jbc.M113.488353","volume":"288","author":"MK Rawal","year":"2013","unstructured":"Rawal, M. K. et al. Insight into pleiotropic drug resistance ATP-binding cassette pump drug transport through mutagenesis of Cdr1p transmembrane domains. J. Biol. Chem. 288, 24480\u201324493 (2013).","journal-title":"J. Biol. Chem."},{"key":"52107_CR25","doi-asserted-by":"publisher","first-page":"3635","DOI":"10.3390\/molecules24203635","volume":"24","author":"E Szepinski","year":"2019","unstructured":"Szepinski, E., Martynow, D., Szweda, P., Milewska, M. J. & Milewski, S. Voriconazole-based salts are active against multidrug-resistant human pathogenic yeasts. Molecules 24, 3635 (2019).","journal-title":"Molecules"},{"key":"52107_CR26","doi-asserted-by":"publisher","first-page":"e0174821","DOI":"10.1128\/AAC.01748-21","volume":"66","author":"M Niimi","year":"2022","unstructured":"Niimi, M., Niimi, K., Tanabe, K., Cannon, R. D. & Lamping, E. Inhibitor-resistant mutants give important insights into Candida albicans ABC Transporter Cdr1 substrate specificity and help elucidate efflux pump inhibition. Antimicrob. Agents Chemother. 66, e0174821 (2022).","journal-title":"Antimicrob. Agents Chemother."},{"key":"52107_CR27","doi-asserted-by":"publisher","first-page":"320","DOI":"10.1007\/BF00352101","volume":"27","author":"R Prasad","year":"1995","unstructured":"Prasad, R., De Wergifosse, P., Goffeau, A. & Balzi, E. Molecular cloning and characterization of a novel gene of Candida albicans, CDR1, conferring multiple resistance to drugs and antifungals. Curr. Genet 27, 320\u2013329 (1995).","journal-title":"Curr. Genet"},{"key":"52107_CR28","doi-asserted-by":"publisher","first-page":"87","DOI":"10.1016\/S0076-6879(02)50957-5","volume":"350","author":"RD Gietz","year":"2002","unstructured":"Gietz, R. D. & Woods, R. A. Transformation of yeast by lithium acetate\/single-stranded carrier DNA\/polyethylene glycol method. Methods Enzymol. 350, 87\u201396 (2002).","journal-title":"Methods Enzymol."},{"key":"52107_CR29","doi-asserted-by":"publisher","first-page":"69","DOI":"10.1016\/j.jsb.2005.01.002","volume":"150","author":"J Lei","year":"2005","unstructured":"Lei, J. & Frank, J. Automated acquisition of cryo-electron micrographs for single particle reconstruction on an FEI Tecnai electron microscope. J. Struct. Biol. 150, 69\u201380 (2005).","journal-title":"J. Struct. Biol."},{"key":"52107_CR30","doi-asserted-by":"publisher","first-page":"331","DOI":"10.1038\/nmeth.4193","volume":"14","author":"SQ Zheng","year":"2017","unstructured":"Zheng, S. Q. et al. MotionCor2: anisotropic correction of beam-induced motion for improved cryo-electron microscopy. Nat. Methods 14, 331\u2013332 (2017).","journal-title":"Nat. Methods"},{"key":"52107_CR31","doi-asserted-by":"publisher","first-page":"216","DOI":"10.1016\/j.jsb.2015.08.008","volume":"192","author":"A Rohou","year":"2015","unstructured":"Rohou, A. & Grigorieff, N. CTFFIND4: Fast and accurate defocus estimation from electron micrographs. J. Struct. Biol. 192, 216\u2013221 (2015).","journal-title":"J. Struct. Biol."},{"key":"52107_CR32","doi-asserted-by":"publisher","first-page":"519","DOI":"10.1016\/j.jsb.2012.09.006","volume":"180","author":"SH Scheres","year":"2012","unstructured":"Scheres, S. H. RELION: implementation of a Bayesian approach to cryo-EM structure determination. J. Struct. Biol. 180, 519\u2013530 (2012).","journal-title":"J. Struct. Biol."},{"key":"52107_CR33","doi-asserted-by":"publisher","first-page":"63","DOI":"10.1038\/nmeth.2727","volume":"11","author":"A Kucukelbir","year":"2014","unstructured":"Kucukelbir, A., Sigworth, F. J. & Tagare, H. D. Quantifying the local resolution of cryo-EM density maps. Nat. Methods 11, 63\u201365 (2014).","journal-title":"Nat. Methods"},{"key":"52107_CR34","doi-asserted-by":"publisher","first-page":"290","DOI":"10.1038\/nmeth.4169","volume":"14","author":"A Punjani","year":"2017","unstructured":"Punjani, A., Rubinstein, J. L., Fleet, D. J. & Brubaker, M. A. cryoSPARC: algorithms for rapid unsupervised cryo-EM structure determination. Nat. Methods 14, 290\u2013296 (2017).","journal-title":"Nat. Methods"},{"key":"52107_CR35","doi-asserted-by":"publisher","first-page":"583","DOI":"10.1038\/s41586-021-03819-2","volume":"596","author":"J Jumper","year":"2021","unstructured":"Jumper, J. et al. Highly accurate protein structure prediction with AlphaFold. Nature 596, 583\u2013589 (2021).","journal-title":"Nature"},{"key":"52107_CR36","doi-asserted-by":"publisher","first-page":"1605","DOI":"10.1002\/jcc.20084","volume":"25","author":"EF Pettersen","year":"2004","unstructured":"Pettersen, E. F. et al. UCSF Chimera\u2013a visualization system for exploratory research and analysis. J. Comput Chem. 25, 1605\u20131612 (2004).","journal-title":"J. Comput Chem."},{"key":"52107_CR37","doi-asserted-by":"publisher","first-page":"486","DOI":"10.1107\/S0907444910007493","volume":"66","author":"P Emsley","year":"2010","unstructured":"Emsley, P., Lohkamp, B., Scott, W. G. & Cowtan, K. Features and development of Coot. Acta Crystallogr. D. Biol. Crystallogr. 66, 486\u2013501 (2010).","journal-title":"Acta Crystallogr. D. Biol. Crystallogr."},{"key":"52107_CR38","doi-asserted-by":"publisher","first-page":"213","DOI":"10.1107\/S0907444909052925","volume":"66","author":"PD Adams","year":"2010","unstructured":"Adams, P. D. et al. PHENIX: a comprehensive Python-based system for macromolecular structure solution. Acta Crystallogr. D. Biol. Crystallogr. 66, 213\u2013221 (2010).","journal-title":"Acta Crystallogr. D. Biol. Crystallogr."},{"key":"52107_CR39","doi-asserted-by":"publisher","first-page":"112","DOI":"10.1107\/S2059798317000067","volume":"73","author":"F Long","year":"2017","unstructured":"Long, F. et al. AceDRG: a stereochemical description generator for ligands. Acta Crystallogr. D. Struct. Biol. 73, 112\u2013122 (2017).","journal-title":"Acta Crystallogr. D. Struct. Biol."},{"key":"52107_CR40","doi-asserted-by":"publisher","first-page":"1074","DOI":"10.1107\/S0907444909029436","volume":"65","author":"NW Moriarty","year":"2009","unstructured":"Moriarty, N. W., Grosse-Kunstleve, R. W. & Adams, P. D. Electronic Ligand Builder and Optimization Workbench (eLBOW): a tool for ligand coordinate and restraint generation. Acta Crystallogr. D. Biol. Crystallogr. 65, 1074\u20131080 (2009).","journal-title":"Acta Crystallogr. D. Biol. Crystallogr"},{"key":"52107_CR41","doi-asserted-by":"publisher","first-page":"12","DOI":"10.1107\/S0907444909042073","volume":"66","author":"VB Chen","year":"2010","unstructured":"Chen, V. B. et al. MolProbity: all-atom structure validation for macromolecular crystallography. Acta Crystallogr. D. Biol. Crystallogr. 66, 12\u201321 (2010).","journal-title":"Acta Crystallogr. D. Biol. Crystallogr."}],"container-title":["Nature Communications"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41467-024-52107-w.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41467-024-52107-w","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41467-024-52107-w.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,9,6]],"date-time":"2024-09-06T06:03:28Z","timestamp":1725602608000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41467-024-52107-w"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,9,6]]},"references-count":41,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2024,12]]}},"alternative-id":["52107"],"URL":"https:\/\/doi.org\/10.1038\/s41467-024-52107-w","relation":{},"ISSN":["2041-1723"],"issn-type":[{"value":"2041-1723","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,9,6]]},"assertion":[{"value":"27 October 2023","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"27 August 2024","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"6 September 2024","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"7722"}}